|Publication number||US4062976 A|
|Application number||US 05/641,730|
|Publication date||Dec 13, 1977|
|Filing date||Dec 18, 1975|
|Priority date||Dec 18, 1975|
|Also published as||CA1052274A1|
|Publication number||05641730, 641730, US 4062976 A, US 4062976A, US-A-4062976, US4062976 A, US4062976A|
|Inventors||Edwin B. Michaels|
|Original Assignee||Michaels Edwin B|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (2), Non-Patent Citations (1), Referenced by (30), Classifications (60), Legal Events (2)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to antimicrobial composition of enhanced efficacy and safety. More particularly, the invention relates to antimicrobial compositions having low toxicity and broad spectrum antimicrobial activity comprising certain amphoteric surfactants which per se have limited antimicrobial use. Still more particularly, the invention is concerned with antimicrobial compositions of enhanced gram positive and gram negative activity comprising in admixture:
A. an alkylsubstituted alanine (0.1 - 40.0 parts, by weight),
B. an alkyl-N,N-dimethylamine oxide, an alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide (0.1 - 40.0 parts, by weight), and
C. a protonating agent, such as hydrochloric acid, acetic acid or citric acid in an amount sufficient to adjust the pH of the overall composition to about 6.0, or below.
The composition of the present invention exhibits sustained periods of antimicrobial activity, particularly in the control of body odor.
As is known, an outstanding method for the control of body odor is to thoroughly wash the body with soap, but so prolific are the microbial flora of the skin that distinctive malodors tend to return within several hours after washing. To provide long periods of protection, there have been developed in the past compositions containing (a) astringents, such as aluminum chlorohydrate, which inhibit apocrine and eccrine gland secretions or (b) antimicrobial agents, such as hexachlorophene and trichlorocarbanilamide. Unfortunately, the former astringent compositions have limited value, since they have little or no control of microbial decomposition of debris and uncontrolled secretions and where there is control of secretions, such use suffers from severe short time limitations to obtain effective control. Nonetheless, the latter antimicrobial compositions have enjoyed widespread use. However, there have been recent investigations into topical and systemic toxicity of the named germicides used to control body odor. These investigations have led to severe restrictions, for instance, on the utilization of hexachlorophene and the recognition of the dangers of other germicides. Further, the use of astringents have only limited utility usually due to its harsh action on skin, particularly, on those who have sensitive skin. If a safe antimicrobial composition of low toxicity could be provided which would inhibit the development of body odor for relatively long periods of time, eg., at least twenty-four (24) hours, or longer, such a composition would satisfy a real need in the art.
It is a principal object of the invention to provide an antimicrobial composition of enhanced efficacy and safety which possesses broad spectrum activity in combating body odor and topical infections. It is a further object of the invention to provide an antimicrobial composition comprising at least an alkylsubstituted alanine surfactant and an alkyl-N,N-dimethylamine oxide or an acylamido t-amine oxide adjusted to a pH of 6.0, or below, so as to control gram positive bacteria, gram negative bacteria, fungi, and yeast, when topically applied. Other objects and advantages will become apparent from a consideration of the ensuing description.
According to the invention, there are provided antimicrobial compositions consisting essentially of a mixture of (a) an alkylsubstituted alanine, and (b) an alkyl-N,N-dimethylamine oxide, or an alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide. The components are admixed at a temperature ranging from about 25° C to 80° C in a substantially aqueous or non-aqueous environment and adjusted to a pH of 6.0, or below, to provide a substantially uniform homogeneous composition having both enhanced broad spectrum activity and low toxicity.
In general, the alkylsubstituted alanine surfactant component of the composition can be written as:
1. RNHCH2 CH2 COOH, or
2. RN(CH2 CH2 COOH)2
where R is a higher alkyl having from 10 to 18 carbon atoms. Illustrative of such substitute alanine derivatives are N-cocoalanine, N-cetylalanine, N-stearylalanine, N-isostearylalanine, N-oleylalanine, N-stearyl-bis (2-aminopropionic acid), N-oleyl-bis (2-aminopropionic acid), N-coco-bis (2-aminopropionic acid), N-cetyl-bis (2-aminopropionic acid), N-lauryl-bis (2-aminopropionic acid), or mixtures of the same.
The alkyl-N,N-dimethylamine oxide, or alkyl-N,N-dihydroxyethylamine oxide, or acylamido t-amine oxide component of the aforementioned mixture, respectively has the respective structure: ##STR1## where R1 is a higher alkyl from 10 to 18 carbon atoms, as for instance, radicals such as decyl, undecyl, lauryl, tridecyl, myristyl, cetyl, stearyl, isostearyl, oleyl or mixtures of the same. Exemplary of the latter amine oxides are decyl-N,N-dimethylamine oxide, lauryl-N,N-dimethylamine oxide, stearyl-N,N-dimethylamine oxide, oleyl-N,N-dimethylamine oxide, cocoamidotrimethylene-N,N-dimethylamine oxide, stearylamidotrimethylene-N,N-dimethylamine oxide, decyl-N,N-dihydroxyethylamine oxide, lauryl-N,N-dihydroxyethylamine oxide, coco-N,N-dihydroxyethylamine oxide, stearyl-N,N-dihydroxyethylamine oxide, oleyl-N,N-dihydroxyethylamine oxide, and mixtures of the same.
In general, the protonating agent necessary to supply the required pH to the overall composition is, for instance, any inert organic or inorganic acid, such as hydrochloric acid, phosphoric acid, sulfuric acid, citric acid, acetic acid, nicotinic acid, and the like. A good operating pH range for the overall composition is 4.0 to 6.0 and, preferably, from about 4.7 to 5.2. The pH of an aqueous solution comprising the above enumerated components of the invention is determined by employing 0.5%, by weight, of active components at a glass electrode to precisely define the acidity of the composition.
In practice, each of the components of the overall composition ranges widely from 0.1 part to 40.0 parts and the balance an inert solvent, such as water or a lower monohydric aliphatic alcohol for a total of at least 100 parts. Where water is employed, small amounts of lower alkyl alcohols may also be added thereto to provide ease in formulation. The pH of the total composition is then adjusted to the requisite pH by adding a suitable inorganic or organic acid thereto. The composition can be employed as a solution or as a spray, such an aerosol spray, utilizing commercially available "Freon" fluorocarbon or equivalent propellant.
Advantageously, the compositions of the present invention possess an extremely low toxicity exhibiting as an LD50 in Swiss-Webster mice greater than four (4) grams per kilogram by intraperitoneal or oral administration. Further, there are observed a lack of primary irritation to the skin and less eye irritation as compared with ordinary soap.
It has been found that the aforementioned compositions can be used in a plurality of ways. For instance, when applied to pyogenic wound infections, rapid healing is promoted. When used as an ear douche, the compositions can relieve ear infections and eliminate those mild microbial infections known as dandruff, crotch itch, athletes foot and the like. As stated above and as shown in the examples hereinbelow set forth, when the compositions of the invention are employed as a general personal body wash, body odor in the axillary and anal/genital areas in particular will be inhibited for periods in excess of twenty-four (24) hours and usually, will exhibit inhibition from seventy-two (72) to ninety-six (96) hours.
In order to facilitate a further understanding of the invention, the following examples are presented primarily for purposes of illustrating certain more specific details thereof. The invention is not to be deemed as limited thereby except as defined in the claims. Unless otherwise noted, all parts and percentages are by weight.
In this example, several compositions are prepared and used as a body wash. Twelve panels each consisting of five men and five women as subjects are selected and supplied with samples of the compositions herein defined in Table I below. After twenty-four (24) hours have elapsed since the panel members' last washing, each is instructed to wash, noting particularly the axillary odor before and after washing. The panel members are then examined during the next twenty-four (24) hours and longer for the time span when typical body odors develop. These times are then noted and recorded in Table I below.
TABLE I__________________________________________________________________________ Average ElapsedPanel Time Body Odor isNo. Composition Detected (hours)__________________________________________________________________________1. Cocoamido-N,N-dimethylamine oxide-12% actives in distilled water (pH=7) 82. Cocoamido-N,N-dimethylamine oxide-12% actives in distilled water - pH adjusted to 5.4 with citric acid 103. N-oleylalanine-12% actives in distilled water - pH measured at 6.2 124. N-cocoalanine-12% actives in distilled water - pH adjusted to 5.4 with citric acid 125. N-cetylalanine-6% in distlled water, plus coco-N,N-dimethylamine oxide-6% in distilled water at pH=6.4 126. N-cocoalanine-6% in distilled water, plus cocoamido-N,N-dimethylamine oxide-6% in distilled water citric acid-0.55% in dis- tilled water at a pH=5. with citric acid 48-967. N-cetylalanine-4% in distilled water, plus myristyl/palmitic-N,N-dimethylamine oxide- 6% in distilled water, adjusted to pH=5 with acetic acid 48-728. N-isostearylalanine-6% in distilled water, plus Oleyl-N,N-dimethylamine oxide-6% in dis- tilled water, adjusted to pH=5.5 with citric acid 48-609. 70/30 Myristyl/palmitic-N,N-dimethylamine oxide-12% in distilled water-pH adjusted to 5.5 with citric acid 1210. Decyl-N,N-dimethylamine oxide-12% actives in distilled water-pH adjusted to 5.2 with acetic acid 811. 70/30 Myristyl/palmitic-N,N-dimethylamine oxide-6% + lauryl-N,N-dimethylamine oxide- 6% in distilled water, adjusted to a pH= 5.2 with citric acid 1012. 70/30 Myristyl/palmitic-N,N-dihydroxyethylamine oxide- 12% actives in distilled water - pH adjusted to 5.1 with citric acid 12__________________________________________________________________________
From the above table, it can be clearly seen that the compositions of the present invention at the adjusted pH range cause a marked improvement in body odor inhibition.
The relation between antimicrobial activity and control of body odor is determined by subjecting each of the panel members of Example 1 to additional washing tests employing the compositions of Example 1. There are obtained the density of microbes in the axillary area of each panelist by using a Rodac plate comprising Tryptose soy agar with TweenŽ 80 and lecithin to neutralize residual germicide. The panelist presses the plate for 30 seconds to the axillary area of the armpit. The plates are then incubated at 37° C for 24 hours and the number of colonies are counted. The density in the colonies per square inch is next calculated. The data obtained are noted in the table below and are the average values of the subjects treated.
TABLE II______________________________________ 0 12 24 48Composition of Hours after Hours after Hours after Hours afterExample 1 washing washing washing washing______________________________________1 1000 2400 TNC* TNC2 1200 2500 TNC TNC3 2800 TNC TNC TNC4 1200 2500 TNC TNC5 1300 2000 TNC TNC6 450 900 1200 17507 200 450 850 1000______________________________________ *TNC means too numerous to count - the density is greater than 3000 colonies per square inch.
There are admixed at 40° C N-stearylalanine (6.25 gm.), coco-N,N-dimethylamine oxide (13 gm.) citric acid (4.5 gm.) and 125 gm. of distilled water. The pH of the mixture when diluted to 0.5% actives is equal to 5.0.
The mixture is tested as a body shampoo and after 60 hours subsequent to washing, the panel reported no evidence of body odor in the axillary areas.
A mixture of N-stearylalanine (6.5 gms.), coco-N,N-dimethylamine oxide (13 gms.), acetic acid (4.5 gms.), and 66 gms. of water, formed at 50° C and having a pH on dilution is equal to 5.1, is employed as a body wash as in Example 3 above. Body odor is absent after seventy-two (72) hours.
Substituting hydrochloric acid for acetic acid in the above mixture, a similar result is noted.
There are admixed N-cetylalanine (2.5 gms.), myristyl-N,N-dimethylamine oxide (5.5 gms.), citric acid (2.0 gms.) and 87 gms. of water. The mixture is heated to 60° C and the pH determined on dilution is 5.5.
As in Example 4 above, the mixture is used as a body wash to determine axillary and pubic body odors. After 72 hours subsequent to washing, no body odor is detected. Moreover, panel members with dandruff report complete control of dandruff after two days' use when washing once each day with the above composition.
A mixture of N-laurylalanine (5.2 gms.), 70/30 myristyl/palmitic-N,N-dimethylamine oxide mixture (5.5 gms.) citric acid (0.7 gms.) and water (108 gms.) is heated to 35° C. The pH of the diluted solution is 5.4 and is used as a body wash. No body odor is detected for seventy-two (72) hours after washing.
There are added at 30° C. 6.2 gms. of N-coco-bis (2-aminopropionic acid), 6.2 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 5. gms. of isopropanol, 0.7 gm. of citric acid, and 92 gms. of water. Upon dilution, the pH measured equals 5.5.
The mixture is used as a body shampoo and controls body odor for 48 hours after washing in all panel members.
There are admixed at 75° C. 10 gms. of N-cetyl-bis (2-aminopropionic acid), 10 gms. of coco-n-betaine, 42 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 15 gms. of isopropanol, 9 gms. of citric acid, and 550 gms. of water. There is obtained a solution having a pH=5.0 on dilution and the preparation when used as a body wash controls odor for more than 72 hours after washing.
This example illustrates the formulation of a solid composition comprising of 32 gms. of N-stearyl-bis (2-aminopropionic acid), 32 gms. of myristyl/palmitic-N,N-dimethylamine oxide, 20 gms. of isopropanol, 40 gms. of water and 6.3 gms. of citric acid. The mixture is vigorously stirred and heated to a temperature of 80° C. Resultant composition is then dried by evaporation and cooled. There is recovered 110 gms. of a waxy solid product having a pH equal to 5.0 at a 0.5% aqueous concentration.
The solid composition is employed as solid detergent for washing and controls body odor for 48 hours after washing.
In this example there is prepared a spray composition. There are admixed 0.1 gm. N-cetyl-bis (2-aminopropionic acid), 0.1 gm. coco-N,N-dihydroxyethylamine oxide, 10 gms. isopropanol, and 0.02 gm. of citric acid. The mixture is heated to 40° C, cooled, and admixed with 100 gms. of liquified butane in a suitable container.
Resultant composition is sprayed under the armpits of several panelists. Each reports underarm odor control for at least 48 hours after use.
There are added to a suitable mixing vessel with stirring 8 gms. of N-cocoalanine, 8 gms. of N-isostearyl- bis (2-aminopropionic acid), 16 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 3.3 gms. of citric acid and q.s. to 250 gms. of water. Resultant mixture is stirred vigorously and heated to 60° C for 15 minutes.
Upon cooling, the pH of the mixture is found to possess a pH equal to 4.7 on dilution.
Resultant composition is employed as a body wash following the procedure of Example 2 above. After 12 hours, it is found by each of five panelists that after 12 hours, no body odor is detected and bacterial count of 190 colonies per square inch is obtained. After 36 hours, no body odor is reported and the bacterial count rose to 600 colonies per square inch. The controls, however, in 36 hours all reported detectable body odor and bacteria colonies too numerous to count, when each of the controls constituting five panelists employs a modified composition of this example in which citric acid is omitted. The pH of the latter composition, on dilution, is 7.4.
Advantageously, the compositions of the present invention, and particularly, as exemplified in each of the above examples, are employed in successfully treating pyogenic infections. The treatment consists of cleaning the wound by washing the same with the composition of the invention and then covering the wound for about 4 to 5 hours. In all cases, irritation and inflammation cease within the four to five hour period, and most wounds exhibit satisfactory healing within two to three days thereafter.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3484523 *||Dec 27, 1966||Dec 16, 1969||Millmaster Onyx Corp||Quaternary ammonium-tertiary amine oxide compositions|
|US3697655 *||Oct 28, 1969||Oct 10, 1972||American Cyanamid Co||Germicidal detergent compositions in controlling dandruff|
|1||Kirk-Othmer Encyc. of Chem. Tech., 2nd Ed., 09231977 19 (1969), pp. 555-566, 575-577.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US4258063 *||Jun 23, 1978||Mar 24, 1981||Henkel Corporation||Self-emulsifying cosmetic base|
|US4839158 *||Jul 31, 1987||Jun 13, 1989||E. B. Michaels Research Associates Inc.||Process and composition for oral hygiene|
|US5059625 *||Oct 1, 1990||Oct 22, 1991||Olin Corporation||Polyglycidol amine oxide surfactants having antimicrobial activity|
|US5266598 *||Aug 11, 1992||Nov 30, 1993||Maruishi Pharmaceutical Co., Ltd.||Skin disinfectant compositions|
|US5275804 *||Sep 25, 1992||Jan 4, 1994||E. B. Michaels Research Associates, Inc.||Process and composition for oral hygiene|
|US5314917 *||Mar 22, 1991||May 24, 1994||E. B. Michaels Research Associates, Inc.||Method for inactivating enveloped viruses and sperm|
|US5389676 *||Sep 13, 1993||Feb 14, 1995||E. B. Michaels Research Associates, Inc.||Viscous surfactant emulsion compositions|
|US5658749 *||Feb 23, 1995||Aug 19, 1997||Corning Clinical Laboratories, Inc.||Method for processing mycobacteria|
|US5968539 *||Jun 4, 1997||Oct 19, 1999||Procter & Gamble Company||Mild, rinse-off antimicrobial liquid cleansing compositions which provide residual benefit versus gram negative bacteria|
|US6004771 *||Aug 11, 1997||Dec 21, 1999||Integrated Research Technology, Llc||Method for processing mycrobacteria|
|US6183757||Jun 4, 1997||Feb 6, 2001||Procter & Gamble Company||Mild, rinse-off antimicrobial cleansing compositions which provide improved immediate germ reduction during washing|
|US6183763||Jun 4, 1997||Feb 6, 2001||Procter & Gamble Company||Antimicrobial wipes which provide improved immediate germ reduction|
|US6190674||Jun 4, 1997||Feb 20, 2001||Procter & Gamble Company||Liquid antimicrobial cleansing compositions|
|US6190675||Nov 12, 1997||Feb 20, 2001||Procter & Gamble Company||Mild, rinse-off antimicrobial liquid cleansing compositions which provide improved residual benefit versus gram positive bacteria|
|US6197315||Jun 4, 1997||Mar 6, 2001||Procter & Gamble Company||Antimicrobial wipes which provide improved residual benefit versus gram negative bacteria|
|US6210695||Jun 4, 1997||Apr 3, 2001||The Procter & Gamble Company||Leave-on antimicrobial compositions|
|US6214363||Nov 12, 1997||Apr 10, 2001||The Procter & Gamble Company||Liquid antimicrobial cleansing compositions which provide residual benefit versus gram negative bacteria|
|US6242486||Oct 10, 1997||Jun 5, 2001||Integrated Research Technology, Llc||Long chain carboxybetaines in antimicrobial formulations|
|US6284259||Nov 12, 1997||Sep 4, 2001||The Procter & Gamble Company||Antimicrobial wipes which provide improved residual benefit versus Gram positive bacteria|
|US6287577||Nov 12, 1997||Sep 11, 2001||The Procter & Gamble Company||Leave-on antimicrobial compositions which provide improved residual benefit versus gram positive bacteria|
|US6287583||Nov 12, 1997||Sep 11, 2001||The Procter & Gamble Company||Low-pH, acid-containing personal care compositions which exhibit reduced sting|
|US6297278||Apr 4, 1994||Oct 2, 2001||Biosyn Inc. (A Pennsylvania Corporation)||Method for inactivating sexually transmitted enveloped viruses|
|US6616922||Mar 27, 2001||Sep 9, 2003||The Dial Corporation||Antibacterial compositions|
|US6770268 *||May 21, 2003||Aug 3, 2004||Oratec Corp.||Non-foaming anti-infective periodontic compositions|
|US7091166 *||Mar 20, 2002||Aug 15, 2006||Henkel Kommanditgesellschaft Auf Aktien||Acidic, phosphate-free plastic cleaner composition with reduced mild steel equipment etch for cleaning plastic parts|
|EP0733361A2 *||Jul 17, 1991||Sep 25, 1996||E.B. Michaels Research Associates, Inc.||Method for inactivating enveloped viruses and sperm|
|WO1987004922A1 *||Feb 17, 1987||Aug 27, 1987||Michaels E B Res Ass Inc||Process and composition for oral hygiene|
|WO1988004315A1 *||Dec 11, 1987||Jun 16, 1988||Wickford Corp New Jersey||Composition for the removal of indelible stains from the human epidermis and the reconditioning and cleaning of processed animal skins|
|WO1992016201A1 *||Jul 17, 1991||Oct 1, 1992||Michaels E B Res Ass||Method for inactivating enveloped viruses and sperm|
|WO2015091163A1 *||Dec 10, 2014||Jun 25, 2015||Henkel Ag & Co. Kgaa||Disinfectant composition with excellent foam profile|
|U.S. Classification||514/561, 510/133, 510/384, 510/503, 510/477, 510/488, 510/433, 510/131, 510/382, 510/480, 514/625, 514/644|
|International Classification||C11D3/00, A01N37/20, A61K31/195, A61Q19/10, A61Q5/02, C11D1/94, A61K31/205, A61Q15/00, A01N37/46, A01N41/04, A01N33/24, C11D3/48, C11D1/75, A01N37/44, A61K8/44, A61K8/40|
|Cooperative Classification||A61K8/40, C11D3/0068, A61Q17/005, A61Q5/02, A61K31/205, A61Q15/00, C11D3/48, A01N33/24, C11D1/75, A01N41/04, A01N37/44, A01N37/20, A61K8/44, C11D1/94, A01N37/46, A61Q19/10|
|European Classification||C11D3/48, A01N41/04, A01N37/46, A01N37/20, A01N37/44, A61K31/205, A61Q15/00, A61K8/40, C11D1/75, A61Q5/02, A61K8/44, C11D1/94, C11D3/00B14, A61Q19/10, A01N33/24, A61Q17/00F|
|Mar 12, 1993||AS||Assignment|
Owner name: E.B. MICHAELS RESEARCH ASSOCIATES, INC., CONNECTIC
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:MICHAELS, EDWIN B.;REEL/FRAME:006457/0695
Effective date: 19930309
|Oct 15, 1996||AS||Assignment|
Owner name: BIOSYN, INC. (A PENNSYLVANIA CORPORATION), PENNSYL
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:E.B. MICHAELS RESEARCH ASSOCIATES, INC. (A CONNECTICUT CORPORATION);REEL/FRAME:008178/0368
Effective date: 19961008